In a so-called Strecker reaction where from an aldehyde compound, ammonia and hydrogen cyanide α-amino nitrile is obtained, when α-amino nitrile that is a product is hydrolyzed, α-amino acid can be readily obtained. Accordingly, the Strecker reaction has long been used in a synthesis process of α-amino acid. However, there are problems in that high toxicity of a cyanide compound that is a raw material and an ammonium salt generated according to a hydrolysis reaction of α-amino nitrile have to be disposed of On the other hand, a so-called amidocarbonylation reaction where, from an aldehyde compound, an amide compound and carbon monoxide, N-acyl-α-amino acid is synthesized has many advantages over the Strecker reaction in that carbon monoxide lower in the toxicity than hydrogen cyanide is used, all raw materials are contained in a product (N-acyl-α-amino acid) to be an atom-economically highly efficient reaction, and furthermore according to a hydrolysis reaction not only an acyl group on nitrogen can be removed and converted into an α-amino acid but also the acyl group can be recovered as carboxylic acid and converted into a corresponding amide to enable to reuse as a raw material. In 1971, Wakamatsu et al found a method of carrying out an amidocarbonylation reaction having such excellent features under pressure of carbon monoxide/hydrogen with cobalt carbonyl that is a transition metal catalyst (non-patent literature 1, patent literature 1).
The Wakamatsu's method generally necessitates high-temperature and high-pressure conditions. On the other hand, in 1997, Beller et al reported an amidocarbonylation reaction that uses a palladium catalyst and a lithium bromide-sulfuric acid cocatalyst (non-patent literature 2, patent literature 2). This is an efficient reaction that does not necessitate hydrogen and can proceed under a lower catalyst amount, a lower carbon monoxide pressure and a lower temperature. Furthermore, Beller et al later reported of the catalyst activities of rhodium, iridium and ruthenium complexes under similar conditions (patent literature 3). Furthermore, more recently, the inventors of the present application found an amidocarbonylation reaction with a platinum catalyst (non-patent literature 3).
On the other hand, from a viewpoint of the organic synthetic chemistry, one of the most useful catalysts is a palladium catalyst. The polymer immobilization thereof has been studied for relatively long periods and many immobilized palladium catalysts have been developed. However, in many of so far developed polymer-immobilized catalysts, since a polymer and a metal portion that is an active center is connected with a ligand, though excellent in the stability, the activity of the catalyst itself is largely affected, and in many cases there is a problem in that the catalyst activity is lowered than that of a corresponding homogeneous system catalyst. Under such circumstances, the inventors of the application have developed a microencapsulated catalyst as a novel polymer-immobilized catalyst. The microencapsulated catalyst immobilizes a metal on a polymer by making use of a physical or an electrostatic interaction, consequently, the catalyst activity rivaling to or exceeding that of the homogeneous catalyst can be expected.
In actuality, the inventors have already developed a microencapsulated Lewis-acid catalyst, a microencapsulated osmium catalyst and a microencapsulated transition metal catalyst (palladium, ruthenium) and have reported that these catalysts worked effectively in various organic synthesis reactions (non-patent literature 4). However, since polystyrene hitherto used as a polymer carrier is dissolved with a reaction solvent in some cases, there is a problem in that the applications thereof are restricted. In this connection, the inventors studied to overcome the problem and developed a palladium catalyst having a novel configuration named as “a polymer Carcerand type (Polymer Incarcerated (PI)) catalyst (non-patent literature 5). In the catalyst, palladium is immobilized to a polymer (1) having an epoxy group and a hydroxyl group on a side chain as shown for instance with a formula below.

More specifically, as shown in a formula below, firstly, palladium is carried or contained by a polymer according to a microencapsulation method, followed by heating under a non-solvent condition to crosslink polymers to render a palladium catalyst that is insoluble in an ordinary solvent. The catalyst effectively worked in a hydrogenation reaction of olefins and an allylic substitution reaction and generated in all cases a corresponding product at a high yield. Furthermore, in all cases, it is confirmed that palladium did not elute off and the catalyst could be recovered and reused.

In this connection, the inventors have studied to make use of features of the novel palladium catalyst as mentioned above to realize the amidocarbonylation reaction method more efficiently and in a clean reaction system.
However, when, according to the report of Beller et al, with NMP (1-methyl-2-pyrolidinone) as a solvent, by use of the above-mentioned novel palladium catalyst: PI Pd (2), a reaction according to a formula below was tried, a yield of N-acyl-α-amino acid of only 9% or less was obtained. In the case of a dioxane solvent, the yield was only several percent.

Non-patent literature 1: J. Chem. Soc., Chem. Commun., 1971, 1540
Non-patent literature 2: Angen. Chem. Int. Ed., 1997, 36, 1494
Non-patent literature 3: Chem. Lett., 2003, 160
Non-patent literature 4: (a) J. Am. Chem. Soc., 1998, 120, 2985. (b) J. Org. Chem., 1998, 63, 6094. (c) J. Am. Chem. Soc., 1999, 121, 11229. (d) Org. Lett., 2001, 3, 2649. (e) Angew. Chem., Int. Ed., 2001, 40, 3469. (f) Angew. Chem., Int. Ed., 2002, 41, 2602. (g) Chem. Commun., 2003, 449
Non-patent literature 5: J. Am. Chem. Soc., 2003, 125, 3412
Patent literature 1: DE-B 2115985 (1971)
Patent literature 2: DE-B 19627717 (1996)
Patent literature 3: DE 100 12251 A1 (1999)